DESCRIPTION The availability of a selective cannabinoid antagonist, SR141716A, has allowed for precipitated cannabinoid withdrawal. The effects of the antagonist on animal behavior and neurochemical release parallel the effects seen following naloxone precipitated morphine withdrawal and have led some researchers to postulate a possible connection between the use of cannabis and the potential for further drug use (Tanda et al., 1997; Rodriguez de Fonseca et al., 1997). As such, an understanding of the mechanism underlying cannabinoid withdrawal may be paramount in attenuating a user's potential for further drug abuse. The aims of the proposed study is to identify the neurobiological substrates involved in and altered by precipitated cannabinoid withdrawal using a variety of behavioral and neuroimaging techniques. Behavioral paradigms sensitive to the motivational effects of withdrawal have been selected to model the negative effective state associated with withdrawal: schedule controlled responding and intra-cranial self-stimulation. The data from these experiments will provide salient dose-time interaction points for [14C]-2- deoxyglucose and CB/1 receptor autoradiography, as well as in situ hybridization histochemistry experiments.